1. Field of the Invention
The present invention relates to a new method for treating or preventing the onset or progression of macular degeneration. More particularly, the invention relates to a new method of treatment which comprises periodic administration of a dosage of glutathione (GSH) enhancing agent alone or in conjunction with other treatments such as anti-oxidant or anti-inflammatory therapy or perhaps commonly known symptomatic treatments.
2. Description of Related Art
Macular degeneration is an age-related eye disease for which there is no known treatment to date that has been shown to be effective at treating or preventing the onset or progression of the disease. Macular degeneration is the leading cause of new blindness in aging individuals, particularly individuals over 65 years of age.
Macular degeneration is a single disorder which is often characterized as one of two types, non-exudative (dry form) or exudative (wet form). Although both types are bilateral and progressive, each type may reflect different pathological processes. An example of a reference which provides a general background for the understanding, identification, and illustration of limited treatments of macular degeneration is Ko, P. and Wong, S., Understanding Macular Degeneration, Hospital Medicine 47-55 (September 1994).
Both exudative (wet form) and non-exudative (dry form) macular degeneration are typically accompanied by the formation of drusen. Drusen are characterized by irregular, discrete, round yellow-white deposits which accumulate in the retina (back of the eye) between the basement membrane of the retinal pigment epithelium (RPE) and the rest of Bruch's membrane. The presence of drusen most likely reflect abnormalities in retinal pigment epithelial function. Drusen deposits can be further categorized into hard drusen or soft drusen. Hard or nodular drusen derive from debris accumulation from retinal pigment epithelial cells in Bruch's membrane. Soft drusen are usually larger than hard drusen and have soft, indistinct margins. Soft drusen are small detachments of the retinal pigment epithelium and presumably derive from diffuse retinal pigment epithelial dysfunction. Soft drusen can also derive from diffuse or confluent drusen, which further derive from a thickening of the inner portion of Bruch's membrane. Calcified drusen are characterized by a glistening appearance and are the consequence of calcification of nodular and diffuse drusen formations.
Non-exudative (dry form) macular degeneration involves atrophy and degeneration of the outer retina, retinal pigment epithelium, Bruch's membrane, and choriocapillaris. The resultant effects of non-exudative macular degeneration are formation of drusen, pigmentary changes, and atrophy. Dysfunction of the retinal pigment epithelium, in particular, leads to the loss of photoreceptors, which are metabolically dependent on the retinal pigment epithelium.
Exudative (wet form) macular degeneration is characterized by serous or hemorrhagic separation of the retinal pigment epithelium or neurosensory layer. Patients may develop choroidal neovascularization, which is manifested as fluid accumulation, hemorrhage, and/or lipid exudation.
These defects typically cause metamorphopsia (distortion) which is detected clinically by Amsler grid testing. An Amsler grid consists of a chart with small squares. When choroidal neovascularization is manifested as fluid accumulation, hemorrhage, and/or lipid exudation the vision is distorted and the lines making up the squares of the grid become blurred and/or wavy.
Choroidal neovascularization occurs by vessels from the choroidal membrane growing through Bruch's membrane into the subretinal pigment epithelial or sub retinal space. This in itself can lead to severe visual loss, however, the retinal pigment epithelium or the neurosensory retina may also detach. Patients with pigment epithelial detachments may develop associated choroidal neovascular membranes. Even with no choroidal neovascular membranes present, 40% of patients with pigment epithelial detachments may continue to experience further loss of vision. Affected patients may exhibit metamorphopsia by Amsler grid testing.
Further consequences of exudative macular degeneration can include tearing of the retinal pigment epithelium and often development of a disciform scar with associated photoreceptor degeneration.
Both of the above-described forms of macular degeneration (non-exudative and exudative) usually proceed continuously toward irreversible loss of central vision. Ultimately, the retina is damaged by long-standing edema, underlying hemorrhage, and/or detachment. Following detachment, the retina may undergo fibrosis, metaplasia, elevation and scarring.
At present there is no one treatment that has proven to be truly effective therapy for treating or preventing the onset or progression of age-related macular degeneration.
There are several types of symptomatic treatment, however, that have been used with limited and isolated success, depending on the particular condition of the patient, to treat exudative (wet form) macular degeneration.
Laser photocoagulation therapy may benefit certain patients with macular degeneration. However, there are high recurrence rates for selected choroidal neovascular membranes which may initially respond to laser therapy. Vision loss may also result from the laser therapy.
Low dose radiation (teletherapy) has also been hypothesized as a possible treatment to induce regression of choroidal neovascularization.
Surgical removal of neovascular membranes is another possible treatment, but it is a highly specialized procedure and reportedly has not had promising results to date.
Interferon-.alpha. is a cytokine that is recognized for its ability to inhibit endothelial cell migration and proliferation in vitro, leukocyte induced androgenesis in animals, and life threatening hemangiomas in children. Interferon-.alpha. has been proposed as a possible drug therapy to inhibit the development of neovascular membranes and thereby decrease foveal destruction and related visual loss. The benefit of interferon-.alpha. therapy, however, is controversial. Even when reported as successful, the benefits of interferon-.alpha. therapy are extremely variable among different individuals and the typically high dose therapy is often associated with negative side effects.
There is presently no effective treatment for non-exudative (dry form) macular degeneration. Management of non-exudative macular degeneration is limited to early diagnosis and careful follow-up to determine if the patient develops choroidal neovascularization. Protection against exposure to ultraviolet light and prescribed dosages of anti-oxidant vitamins (e.g., vitamin A, .beta.-carotene, lutein, zeaxanthin, vitamin C and vitamin E) and zinc may also be of some benefit, but as yet these treatments remain unproven. Additionally, the use of zinc has shown appreciable negative side effects including effects on heart disease and induction of copper deficiency anemia.
A method of treatment which effectively treats or prevents the onset or progression of this debilitating ocular disorder would be of considerable benefit. An effective method of treatment is especially needed to control the dry form of macular degeneration which afflicts 90% of the patients. Additionally, it has been estimated that most of the 1 million people identified as visually handicapped in Britain have macular degeneration and more than 10 million cases of the disease now exist in the U.S. Other studies suggest that 10% of the United States population between ages 65 to 74 and 30% of the population exceeding 75 years of age develop signs of macular degeneration in one form or the other.